US7180056B2 - Mass spectrometry and mass spectrometry system - Google Patents

Mass spectrometry and mass spectrometry system Download PDF

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US7180056B2
US7180056B2 US11/143,717 US14371705A US7180056B2 US 7180056 B2 US7180056 B2 US 7180056B2 US 14371705 A US14371705 A US 14371705A US 7180056 B2 US7180056 B2 US 7180056B2
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peak
peaks
mass spectrometry
stage
mass
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US20050274884A1 (en
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Atsushi Ohtake
Kinya Kobayashi
Kiyomi Yoshinari
Toshiyuki Yokosuka
Atsumu Hirabayashi
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Hitachi Ltd
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6848—Methods of protein analysis involving mass spectrometry
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0027—Methods for using particle spectrometers
    • H01J49/0031—Step by step routines describing the use of the apparatus
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/13—Tracers or tags
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation

Definitions

  • the present invention relates to mass spectrometry and a mass spectrometry system, and in particular, to a mass spectrometer and a system for analyzing a mass spectrum in which biopolymeric substances such as protein, polypeptide, sugar, and nucleic acid are identified and are quantitatively determined with high precision and high throughput.
  • samples including a first sample and a second sample are obtained respectively from two test bodies, i.e., a first test body and a second test body.
  • the first sample is bonded or combined with a “light reagent” and the second sample is combined with a “heavy reagent”.
  • the heavy and light reagents are equal in chemical structure. However, these reagents differ in the mass number from each other and hence are different in the molecular weight from each other.
  • first and second samples When the first and second samples are mixed with each other and the mixture is measured by a mass spectrometer, there appear a pair of peaks apart from each other by difference ( ⁇ m) between the molecular weight values. If the first and second protein samples are attained respectively from the same test body and the samples are substantially equal in density and quantity to each other, the two peaks associated with the respective samples have substantially the same intensity. However, if a first sample is obtained from a sick test body and a second sample is attained from a healthy test body, there possibly appear a pair of peaks having mutually different peak intensity depending on cases.
  • the techniques using isotope labeling have been described in many articles, for example, JP-A-2003-107066 and Japanese Patent No. 3345401.
  • the articles describe a method in which a reagent marked by an isotope is added to a measuring sample and the sample is analyzed by a tandem mass spectrometer capable of achieving multistage dissociation and measurement.
  • a tandem mass spectrometer capable of achieving multistage dissociation and measurement.
  • MS 1 intensity ratio of the peak pair detected through a first-stage measurement
  • MS 2 second-stage measurement
  • the tandem mass spectrometer can achieve multistage dissociation and measurement through one measuring session.
  • peaks measured by MS 1 peaks required to identify an amino acid array are selected to conduct MS 2 .
  • database retrieval an amino acid array corresponding to the MS 2 spectrum measured by MS 2 is determined.
  • the mass number associated with the “necessary peak” is known, a peak to be selected by MS 1 can be registered to the apparatus. Therefore, the dissociation and measurement up to MS 2 can be automatically carried out through one session.
  • MS 1 is first conducted to select a peak for MS 2 . That is, the MS 2 spectrum is acquired through measurement in the second session.
  • a liquid chromatograph (to be abbreviated as LC hereinbelow) is installed in a stage preceding the mass spectrometer. Constituent elements or components flown from the LC are used as a sample for the mass spectrometer. In the separation by the LC, a period of time of several seconds is required to obtain the elements to be measured depending on cases. The elements flow from a column of the LC for about ten seconds to 20 seconds.
  • the MS 1 results are analyzed and the peak obtained by MS 2 is judged within the period of about ten seconds to 20 seconds, the time-consuming separation is required to be conducted by the LC. Additionally, since it is likely that composition of the constituent elements for the measurement vary between when the flow of the elements is started and when the flow thereof is stopped. Consequently, the peak thus measured is favorably selected within a period of time from about 0.1 second to one second.
  • the present invention provides a technique and associated devices and methods as below.
  • a mass spectrometry including the steps of preparing a sample including a plurality of test bodies respectively labeled with reagents having mutually different molecular weights, separating constituent elements from the sample by chromatography, conducting a mass spectrometric analysis for the constituent elements by a tandem mass spectrometer capable of multistage dissociation and measurement, analyzing a result of the mass spectrometric analysis in a realtime fashion, and using in a realtime fashion a result of the analysis of at least one test body for a mass spectrometric analysis of other test bodies.
  • a mass spectrometry system including a chromatograph for developing a sample including a plurality of test bodies respectively labeled with a plurality of isotope reagents, a tandem mass spectrometer connected to the chromatograph, the spectrometer being capable of conducting multistage dissociation and measurement; a unit for placing or moving the sample in an analysis area of the tandem mass spectrometer, an information processor for analyzing in a realtime fashion a result of the mass spectrometric analysis by the spectrometer, a controller for controlling the chromatograph and the tandem mass spectrometer, and an input/output device for inputting necessary information to the controller and/or outputting necessary information from the controller.
  • the chromatograph may be a liquid or gas chromatography apparatus.
  • Realtime data analysis as well as changes and modifications of a mass spectrometry condition according to the data analysis are favorably achieved within at most one second, particularly favorably, within 0.1 second.
  • the identification and quantitative determination of biopolymer can be conducted with high throughput using a tandem mass spectrometer.
  • FIG. 1 is a block diagram schematically showing a first embodiment of a mass spectrometry system of the present invention.
  • FIG. 2 is a flowchart to explain a mass spectrometry used in an embodiment of the present invention.
  • FIG. 3 is a spectral graph obtained through MS 1 using mass spectrometry in an embodiment of the present invention.
  • FIG. 4 is a flowchart showing a spectral pairing procedure in an embodiment of a mass spectrometry system of the present invention.
  • FIG. 5 is a diagram showing an example of a display screen image in an embodiment of a mass spectrometry system of the present invention.
  • FIG. 6 is a schematic block diagram showing a second embodiment of a mass spectrometry system of the present invention.
  • FIG. 7 is a diagram showing an example of a display screen image to select a judging expression in an embodiment of a mass spectrometry system of the present invention.
  • FIG. 8 is a spectral graph obtained using mass spectrometry in an embodiment of the present invention in which spectral groups are separated from each other.
  • FIG. 9 is a spectral graph obtained using mass spectrometry in an embodiment of the present invention in which spectral groups overlap with each other.
  • mass spectrometry and a mass spectrometry system in which a sample prepared by mixing a plurality of test bodies respectively labeled by reagents different in molecular weight from each other is measured by a tandem mass spectrometer.
  • the system includes a tandem mass spectrometer capable of at least multistage dissociation and measurement, an information processor, and an input/output device. Therefore, a sample marked with an isotope can be identified and quantitatively determined at a high speed.
  • a mass spectrometry and a mass spectrometry system in which an information processor analyzes in a realtime fashion a result of spectral measurement in a first-stage of the measurement by the tandem mass spectrometer capable of conducting a multistage dissociation and measurement.
  • an information processor analyzes in a realtime fashion a result of spectral measurement in a first-stage of the measurement by the tandem mass spectrometer capable of conducting a multistage dissociation and measurement.
  • ions for dissociation in second-stage and subsequent-stage measurement are selected in a realtime fashion.
  • peaks necessary to identify a sample are determined by MS 1 , and structure of an object of measurement is clarified using spectra obtained by MS 2 or subsequent dissociation and measurement (MS n , n>2). If peaks necessary for the measurement are known in advance, MS 2 (or, MS n , n>2) can be conducted through one session using functions of the tandem MS. However, if such peaks are unknown, after analyzing MS 1 spectra, it is required to additionally conduct one measurement session. On the other hand, according to the present invention, peaks to be measured are extracted from MS 1 spectra during the measuring session in a realtime fashion to thereby conduct MS 2 . As a result, even for an unknown sample, the analysis, identification, and quantitative determination thereof can be achieved through at least one measuring session, and hence throughput of measurement is remarkably increased.
  • a mass spectrometry and a mass spectrometry system in which the isotope reagents for the labeling include two isotope reagents which are equal in molecular weight to each other and which are different in chemical structure from each other and the sample is a mixture including two test bodies labeled by the isotope reagents.
  • the isotope reagents for the labeling include two isotope reagents which are equal in molecular weight to each other and which are different in chemical structure from each other and the sample is a mixture including two test bodies labeled by the isotope reagents.
  • a mass spectrometry and a mass spectrometry system includes the steps of assuming that molecular weight difference between the two isotope reagents is ⁇ m, extracting from spectra obtained through first-stage measurement a pair of peaks apart from each other by n ⁇ m, where z is electric charge of an ion and n is a positive integer, and selecting, on the basis of a mutual relationship between spectral intensity of an extracted peak pair, a peak to be measured in second-stage and subsequent-stage measurement.
  • a pair of peaks can be selected at a high speed.
  • a mass spectrometry and a mass spectrometry system includes the steps of assuming that the mass spectrometer has a mass number measuring error indicated by ⁇ , and treating, as pairs of peaks, all peaks in a range of ⁇ of a value m/z of a peak in consideration and peaks in a range from (a mass number of the peak in consideration ⁇ n ⁇ m/z+ ⁇ ) to (the mass number of the peak in consideration ⁇ n ⁇ m/z ⁇ ). It is therefore possible to conduct the analysis in consideration of a mass spectrometric error of a mass spectrometer.
  • a mass spectrometry system in which the peak pair extraction utilizes the steps of starting extraction of a pair of peaks beginning at a peak selected from spectra measured in the peak pair extraction, the peak having a maximum value of m/z, and extracting thereby a pair of peaks in a descending m/z order.
  • a mass spectrometry system which uses the steps of assuming in the peak pairs that intensity of a peak labeled by an isotope having a large mass number is P 1 , intensity of a peak labeled by an isotope having a small mass number is P 2 , and r takes a value set by a measuring operator, wherein a piece of a pair of peaks or both thereof satisfying a judging expression P 1 /P 2 >r or P 1 /P 2 ⁇ r is or are dissociated in second-stage and subsequent-stage measurement. Therefore, the peak judgment can be mechanically conducted using a judging expression, and hence peaks to be measured in second-stage and subsequent-stage measurement can be determined by an information processor at a high speed.
  • a mass spectrometry and a mass spectrometry system includes the steps of accumulating all intensity values of peaks in a range of ⁇ of a value m/z of a peak in consideration labeled by an isotope having a large mass number and thereby obtaining P 1 as a result of the accumulation, wherein accumulating all intensity values of peaks in a range of ⁇ of a value m/z of a peak in consideration labeled by an isotope having a small mass number and thereby obtaining P 2 as a result of the accumulation.
  • the analysis can be therefore conducted in consideration of a mass spectrometric error of MS.
  • a mass spectrometry and a mass spectrometry system includes the steps of assuming that the judging expression is P 1 ⁇ P 2 >r 2 or P 1 ⁇ P 2 ⁇ r 2 and r 2 takes a value set by the measuring operator, wherein a piece of a pair of peaks or both thereof satisfying the judging expression is or are dissociated in second-stage and subsequent-stage measurement. Therefore, the peak judgment can be mechanically conducted using a judging expression, and hence peaks to be measured in second-stage and subsequent-stage measurement can be determined by an information processor at a high speed.
  • a mass spectrometry and a mass spectrometry system includes the steps of assuming the judging expression is P 1 ⁇ P 2 >r 3 or P 1 'P 2 ⁇ r 3 and r 3 takes a value set by the measuring operator, wherein a piece of a pair of peaks or both thereof satisfying the judging expression is or are dissociated in second-stage and subsequent-stage measurement. Therefore, the peak judgment can be mechanically conducted using a judging expression, and hence peaks to be measured in second-stage and subsequent-stage measurement can be determined by an information processor at a high speed.
  • a mass spectrometry and a mass spectrometry system includes the steps of assuming the judging expression is r 4 >P 1 /P 2 >r 5 and r 4 and r 5 take values set by the measuring operator, wherein a piece of a pair of peaks or both thereof satisfying the judging expression is or are dissociated in second-stage and subsequent-stage measurement. Therefore, the peak judgment can be mechanically conducted using a judging expression, and hence peaks to be measured in second-stage and subsequent-stage measurement can be determined by an information processor at a high speed.
  • a mass spectrometry system utilizes the steps of arbitrarily setting the judging expression by the measuring operator, wherein a piece of a pair of peaks or both thereof satisfying the judging expression is or are dissociated in second-stage and subsequent-stage measurement. Therefore, the peak judgment can be mechanically conducted using a judging expression, and hence peaks to be measured in second-stage and subsequent-stage measurement can be determined by an information processor at a high speed.
  • the test body as an object of measurement is protein, peptide obtained by decomposing protein, chemically modified peptide, sugar, or nucleic acid. It is therefore possible to conduct the identification and the quantitative determination of general biopolymer.
  • a mass spectrometry and a mass spectrometry system includes the steps of using, when labeling protein, peptide obtained by decomposing protein, or chemically modified peptide, an isotope reagent which specifically bonds with cystine or tryptophane contained in the protein or peptide obtained by decomposing the protein, or the chemically modified peptide.
  • the isotope reagent is an isotope of hydrogen, an isotope of oxygen, an isotope of carbon, an isotope of nitrogen, an isotope of phosphorus, or a combination thereof.
  • an optimal reagent labeled by an isotope can be selected.
  • the mass spectrometry system includes an information processor for conducting database retrieval and either one of or both of a network connecting device and a data storage. This increases the database retrieval speed, and an object of measurement can be identified and quantitatively determined during the measurement in a realtime fashion.
  • the system shown in FIG. 1 includes a sample introducing system 101 , a liquid chromatograph (LC) 102 , a tandem mass spectrometer (MS) 103 , a control unit 104 , a computer 201 , a display 202 as an output device, a keyboard 203 as an input device, and signal lines connecting the constituent components to each other.
  • the system of the embodiment shown in FIG. 1 operates according to a flowchart of FIG. 2 .
  • the system operation of the embodiment will be described. Assume that protein identification and quantitative determination are conducted for two test bodies A and B.
  • the test bodies A and B are extracted from the same tissue of animals of the same kind and are equal in density and quantity to each other. However, the individual items A and B are separated from each other.
  • the object of the analysis is to determine difference in protein manifestation and identification of the protein according to the individual items.
  • the test bodies A and B are labeled by two isotope reagents a and b.
  • the reagents a and b are equal in chemical composition to each other, but differ in the number of carbon isotope (C 12 and C 13 ) from each other. While the constitution of the reagent a includes eight C 13 , the constitution of the reagent b includes only C 12 .
  • the molecular weight of reagent a is more than that of the reagent b by eight.
  • the reagents a and b have a property to bond or couple with only cysteine residues in protein.
  • the test bodies A and B are decomposed by a digestive enzyme. Samples of an equal quantity derived from the decomposition of the test bodies A and B are mixed with each other and the mixed sample is set to the sample introducing system 101 . The sample from the system 101 is separated by the liquid chromatograph 102 to be fed to the tandem mass spectrometer 103 .
  • the controller 104 controls operation of the units 102 and 103 .
  • the computer 201 controls the controller 104 .
  • the computer 201 issues an indication to the controller 104 according to a measuring condition beforehand designated by the measuring operator from the keyboard 203 .
  • the computer 201 records MS 1 spectral data obtained from the chromatograph 102 and the mass spectrometer 103 .
  • the spectral graph of FIG. 3 includes main peaks 21 to 25 . The distance between the peaks 21 and 22 is 8.2 Da and that between the peaks 24 and 25 is 7.8 Da.
  • the computer 210 carries out spectral pairing on the basis of the mass measurement error ⁇ of the spectrometer 103 and the mass difference ⁇ m between the reagents a and b.
  • the pairing is generally conducted in a procedure indicated by a flowchart of FIG. 4 . Referring now to the flowchart of FIG. 4 , description will be given of a procedure to extract a peak pair from the spectral data shown in FIG. 3 . Unless otherwise designated by the measuring operator, the pairing is conducted beginning at a highest peak of m/z. In the case of FIG. 3 , the operation is initiated beginning at the peak 21 .
  • the mass number of the peak 21 is 1510.1.
  • a search is made for peaks in a range of ⁇ from the peak 21 , that is, for m/z in a range from 1509.6 to 1510.1. Obtained peaks are recorded as peaks belonging to the peak 21 . Intensity of each peak belonging to the peak 21 is accumulated and the accumulated result is recorded as a value of P 1 of the peak 21 .
  • a search is made for peaks in an area ranging from 1510.1 ⁇ n ⁇ m/z ⁇ to 1510.1 ⁇ n ⁇ m/z+ ⁇ .
  • the peak 22 meets the condition, and hence the peaks 21 and 22 are registered as a peak pair. Intensity of each peak belonging to the peak 22 is accumulated and the accumulated result is stored as P 2 of the peak 22 .
  • the peak 23 is detected. Since no peak near the peak 23 can be paired therewith, the search is made in an area by widening the area toward a smaller value of m/z without conducting the pairing of the peak 23 .
  • peaks in the area expressed as m/Z ⁇ of the peak 24 belong to the peak 24 .
  • intensity of each peak belonging to the peak 24 is accumulated and the accumulated result is stored as P 1 of the peak 24 .
  • a search is made for peaks in an area from 1146.6 ⁇ n ⁇ m/z ⁇ to 1146.6 ⁇ n ⁇ m/z+ ⁇ . This results in detection of the peak 25 , and hence the peaks 24 and 25 are registered as a peak pair. Intensity of each peak belonging to the peak 25 is accumulated and the accumulated result is stored as P 2 of the peak 25 .
  • the search is continuously carried out. Since there exists no peak for m/z less than an m/z value associated with the peak 25 in the embodiment, the search is terminated at this point. If no peak pair is detected by the termination of the search, the measurement of the MS 2 spectrum is not carried out. After next constituent has flown from the chromatograph, acquisition of the MS 1 spectrum is carried out again for the constitution.
  • a threshold value such that a peak with intensity equal to or less than the threshold value is not used for the peak pair search.
  • the system selects an MS 1 peak to be measured according to a relationship between the intensity P 1 of the peak derived from the test body A and the intensity P 2 of the peak derived from the test body B.
  • P 1 /P 2 1.1 for the peaks 21 and 22 and hence the peaks 21 and 22 do not satisfy the judging expression.
  • P 1 /P 2 0.6 and the expression is satisfied.
  • the peaks 24 and 25 are determined as peaks for the MS 2 measurement, and hence an m/z value is recorded for each of the peaks 24 and 25 . If a plurality of peaks are determined, an m/z value is recorded for each thereof. A period time from when the result of the MS 2 measurement is obtained to when the peaks are determined is at most 0.1 second even when a general personal computer is used.
  • the MS 2 measurement is conducted for the selected peaks. Since two selected peaks exist for each peak pair, the MS 2 measurement is conducted for either one or both of the peaks. In the embodiment, the MS 2 measurement is conducted for only the peak labeled by a light isotope, i.e., the peak 25 .
  • FIG. 5 shows an example of information items displayed on the display 202 .
  • the example includes the following items.
  • the measurement operator can arbitrarily display information items such as a measuring condition and a database search condition on the display 202 .
  • the database search possibly requires a period of time ranging from several minutes to several hours depending on cases. Therefore, the search and the measurement are concurrently carried out. This means that it does not usually occur that after a search operation is finished, a subsequent measuring operation is conducted.
  • the tandem MS 103 conducts the MS 2 measurement for all selected peaks (part of the selected peaks when the operator designates a desired mode for measurement). After subsequent constitution flows from the LC, the MS 103 starts again MS 1 spectral measurement.
  • proteins having difference in occurrence between individual bodies or items can be particularly identified. Also, since the operation including the MS 1 measurement, the MS 2 measurement, and the database retrieval can be achieved through one session of measurement, the identification and the quantitative determination of protein can be carried out with high throughput.
  • FIG. 6 description will be given of an embodiment of a mass spectrometry system according to the present invention.
  • the system shown in FIG. 6 is implemented by connecting a cluster computer 204 , a data storage 205 , and a network server 206 to the system of FIG. 1 .
  • the system of FIG. 6 is basically equal in operation to that of FIG. 1 , but there exists difference therebetween as below.
  • the spectral data obtained through the MS 2 measurement is processed by the cluster computer 204 , not by the computer 201 .
  • the database is not included in the computer 201 , but is stored in a high-speed data storage 205 having large storage capacity. Thanks to the network server 206 , a database on an external network can be used.
  • the first embodiment employs P 1 /P 2 ⁇ r as the judging expression, there may be used judging expressions as follows.
  • the condition of (1) is used when P 1 /P 2 >r obviously holds.
  • the condition of (2) is used when there exists spectral intensity difference.
  • the condition of (3) is used when a spectral intensity product is significant.
  • the condition of (4) is used to confirm whether or not proteins contained in two test bodies A and B are associated with peaks actually derived from the same protein.
  • the identification and the quantitative determination of proteins can be carried out with high throughput through one session of measurement as in the first embodiment.
  • the similar advantage can also be obtained by using a combination of the above judging expressions.
  • a condition is set for the judging expression by the computer 201 , the display 202 , and the keyboard 203 shown in FIG. 1 .
  • an input screen image is presented on the display 202 as shown in FIG. 7 .
  • the input screen image includes a check box 51 , a judging expression 52 , a judging value input field 53 , an AND/OR setting field 54 , and a particular judging expression input field 59 .
  • the measuring operator checks a judging expression check box 51 for a desired judging expression and then inputs a judging value in an associated input field 53 .
  • the AND/OR setting field 54 is used.
  • the operator selects AND. If either one thereof is to be satisfied, the operator selects OR.
  • the operator inputs the judging expression in the field 59 . After the input items are completely set in the screen, the operator depresses Decision or Execute button to thereby actually set the judging expression. If the designated judging expressions conflict with each other, a warning message is displayed. The operator conducts again an input operation to set a judging expression.
  • the embodiment it is possible to combine a plurality of judging expressions or to designate a particular judging expression. Using the judging expressions described above, the identification and the quantitative determination can be carried out with high throughput as in the above embodiments.
  • the test bodies A and B may be protein, chemically modified peptide, sugar, or nucleic acid.
  • the test bodies are sugar, there is used an isotope reagent which specifically bonds or combines with a particular monosacharide.
  • the test bodies are nucleic acid, there is used an isotope reagent which specifically bonds with a particular base or a particular base array.
  • the samples to be measured are general biopolymer, structure thereof can be identified and quantity thereof can be determined with high throughput through one measuring session.
  • FIG. 8 shows an example of a MS 1 spectral graph obtained using an isotope reagent which bonds with an amino acid residue having a high existing quantity.
  • Peptide chains measured and presented in FIG. 8 include amino acid residues bonded with a plurality of isotope reagents. Therefore, while only one paired peak appears in the first embodiment, two or more peaks appear for a peak pair in the sixth embodiment.
  • peaks 81 to 83 and 91 to 93 are derived from the test body A of the first embodiment
  • peaks 84 and 94 are derived from the test body B.
  • the general isotope reagent is a regent containing an isotope of carbon or hydrogen.
  • the similar advantageous effect can be obtained by use of a reagent containing an isotope of oxygen, an isotope of carbon, an isotope of nitrogen, an isotope of phosphorus, or a reagent containing a combination thereof.

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US20070195773A1 (en) * 2006-02-21 2007-08-23 Tatar Mohammed I Pipelined packet switching and queuing architecture
US20070221836A1 (en) * 2006-03-24 2007-09-27 Kinya Kobayashi Mass analysis system
US20080283740A1 (en) * 2007-05-16 2008-11-20 Hitachi, Ltd Mass spectrometry system and mass spectrometry method
US20100181471A1 (en) * 2009-01-21 2010-07-22 Pop Julian J Downhole mass spectrometry

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